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Review
, 10, 2495-517
eCollection

Comparative Efficacy of Long-Acting Muscarinic Antagonist Monotherapies in COPD: A Systematic Review and Network Meta-Analysis

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Review

Comparative Efficacy of Long-Acting Muscarinic Antagonist Monotherapies in COPD: A Systematic Review and Network Meta-Analysis

Afisi Segun Ismaila et al. Int J Chron Obstruct Pulmon Dis.

Abstract

Background: Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).

Methods: A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George's Respiratory Questionnaire score, and rescue medication use.

Results: Twenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL [104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL [123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St George's Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to -2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]); 24-week transitional dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00 [0.49-1.51]); and 24-week rescue medication use (data not available; -0.41 puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0.74 to -0.30]; -0.30 puffs/day [-0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were -12.8 mL (-39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (-7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (-11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (-11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (-5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (-15.30 to 54.38), umeclidinium versus glycopyrronium. Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.

Conclusion: The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard. Choice should depend on physician's and patient's preference.

Keywords: anticholinergics; bronchodilator; meta-analysis; muscarinic antagonist; systematic review.

Figures

Figure 1
Figure 1
Flow chart of study selection process. Abbreviations: CDSR, Cochrane Database of Systematic Review; CENTRAL, Cochrane Central Register of Controlled Trials; CSR, clinical study report; DARE, Database of Abstracts of Reviews of Effects; EU-CTR, EU Clinical Trials Register; HTA, Health Technology Assessment; NMA, network meta-analysis; PROSPERO, International Prospective Register of Systematic Reviews; SLR, systematic literature review; WHO ICTRP, World Health Organization International Clinical Trials Registry Platform.
Figure 2
Figure 2
Overall network of studies in the network meta-analysis of umeclidinium versus other LAMAs or placebo for (A) trough FEV1 at 12 weeks, (B) trough FEV1 at 24 weeks, (C) SGRQ total score at 24 weeks, (D) TDI focal score at 24 weeks, and (E) rescue medication use at 24 weeks. Note: Gray italic text indicates studies that did not report measures of uncertainty. Abbreviations: BD, twice-daily; FEV1, forced expiratory volume in 1 second; LAMA, long-acting muscarinic antagonist; OD, once-daily; PBO, placebo; SGRQ, St George’s Respiratory Questionnaire; TDI, transitional dyspnea index.
Figure 3
Figure 3
Differences in intervention versus the comparator for change from baseline in (A) trough FEV1 (mL) at 12 weeks, (B) trough FEV1 (mL) at 24 weeks, (C) SGRQ total scores at 24 weeks, (D) TDI focal scores at 24 weeks, and (E) rescue medication use at 24 weeks (95% CrI and probability of the intervention being better than the comparator). Abbreviations: CrI, credible interval; FEV1, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; TDI, transitional dyspnea index.

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